This section introduces aspects that may help facilitate a better understanding of the disclosure. Accordingly, these statements are to be read in this light and are not to be understood as admissions about what is or is not prior art.
In the production of pharmaceutical products, there is strong potential for batch contamination related to the presence of residual materials such as active ingredients, cleaning agents, microorganisms, dust and particulates. Cleaning validation provides documented evidence that the cleaning processes used have cleaned to predefined limits. The goal is to prevent contamination that can influence the safety, efficacy, purity and quality of manufactured products.
After the production process, the reaction or mixing vessel is cleaned by a prescribed method that may involve a series of solvents and/or cleaning agents or acidic, alkaline and/or surfactant solutions. Any one of those may leave residual material, and there could be an accumulation of materials on the surface once the “cleaning” process is complete. Pharmaceutical organizations must determine whether residual materials are present, and if so, how are they are represented on the surface. One of the most common surfaces is stainless steel and the characteristics of that surface (polished or brushed or roughened) can dictate how the materials adhere. Laboratory experiments with cleaned brushed stainless steel surfaces have indicated that residues from solid compounds deposited from solvents tend to exist as “islands” of material and not a continuous thin coating, due to the coalescing of materials during the evaporation process and nucleation around surface features and “dust particles”.
It is essential to avoid cross-contamination during the manufacture of active pharmaceutical ingredients. Significant costs are associated with cleaning large reaction vessels used to prepare these substances and even greater costs in validating their cleanliness. The FDA has approved certain procedures for validation which involve manual swabbing and then liquid chromatography/mass spectrometry analysis of the swabbed materials (“Guidance for Industry: Analytical Procedures and Methods Validation for Drugs and Biologics”, FDA, Rockville, Md., 2014). Large areas must be examined and the off-line mass spectrometry analysis is time-consuming (K Burson, et al., Pharmaceutical Technology, 2014). The lack of association of the cleaning/sampling step with the analytical step, in time and in place, is a significant problem with this approach (H. A. Pawar, et al., Int. J. Pharm. Phytopharmacol. Res. 1 (2011) 8-16). Attempts have been made to perform ambient ionization, specifically desorption electrospray ionization, on surfaces and to use this method to validate cleaning (S. Soparawalla, et al., Rapid Commun. Mass Sepctrom. 23 (2009), 131-137). However, there has been limited success with this approach. The described methods are cost intensive techniques that provide an averaged or integrated result and do not necessarily represent the surface or how materials are distributed over the surface.